The G-protein-coupled estrogen receptor agonist G-1 suppresses proliferation of ovarian cancer cells by blocking tubulin polymerization

The G-protein-coupled estrogen receptor 1 (GPER) has recently been reported to mediate the non-genomic action of estrogen in different types of cells and tissues. G-1 (1-[4-(6-bromobenzo[1,3] dioxol-5yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinolin-8-yl]-ethanone) was developed as a potent and selective agonist for GPER. G-1 has been shown to induce the expression of genes and activate pathways that facilitate cancer cell proliferation by activating GPER. Here we demonstrate that G-1 has an anticancer potential with a mechanism similar to vinca alkaloids, the commonly used chemotherapy drugs. We found that G-1 blocks tubulin polymerization and thereby interrupts microtubule assembly in ovarian cancer cells leading to the arrest of cell cycle in the prophase of mitosis and the suppression of ovarian cancer cell proliferation. G-1 treatment also induces apoptosis of ovarian cancer cells. The ability of G-1 to target microtubules to suppress ovarian cancer cell proliferation makes it a promising candidate drug for treatment of ovarian cancer.     

Airport detection in remote sensing images: a method based on saliency map

The detection of airport attracts lots of attention and becomes a hot topic recently because of its applications and importance in military and civil aviation fields. However, the complicated background around airports brings much difficulty into the detection. This paper presents a new method for airport detection in remote sensing images. Distinct from other methods which analyze images pixel by pixel, we introduce visual attention mechanism into detection of airport and improve the efficiency of detection greatly. Firstly, Hough transform is used to judge whether an airport exists in an image. Then an improved graph-based visual saliency model is applied to compute the saliency map and extract regions of interest (ROIs). The airport target is finally detected according to the scale-invariant feature transform features which are extracted from each ROI and classified by hierarchical discriminant regression tree. Experimental results show that the proposed method is faster and more accurate than existing methods, and has lower false alarm rate and better anti-noise performance simultaneously.     

Isoflurane Preconditioning Confers Cardioprotection by Activation of ALDH2

The volatile anesthetic, isoflurane, protects the heart from ischemia/reperfusion (I/R) injury. Aldehyde dehydrogenase 2 (ALDH2) is thought to be an endogenous mechanism against ischemia-reperfusion injury possibly through detoxification of toxic aldehydes. We investigated whether cardioprotection by isoflurane depends on activation of ALDH2.Anesthetized rats underwent 40 min of coronary artery occlusion followed by 120 min of reperfusion and were randomly assigned to the following groups: untreated controls, isoflurane preconditioning with and without an ALDH2 inhibitor, the direct activator of ALDH2 or a protein kinase C (PKCε) inhibitor. Pretreatment with isoflurane prior to ischemia reduced LDH and CK-MB levels and infarct size, while it increased phosphorylation of ALDH2, which could be blocked by the ALDH2 inhibitor, cyanamide. Isolated neonatal cardiomyocytes were treated with hypoxia followed by reoxygenation. Hypoxia/reoxygenation (H/R) increased cardiomyocyte apoptosis and injury which were attenuated by isoflurane and forced the activation of ALDH2. In contrast, the effect of isoflurane-induced protection was almost abolished by knockdown of ALDH2. Activation of ALDH2 and cardioprotection by isoflurane were substantially blocked by the PKCε inhibitor. Activation of ALDH2 by mitochondrial PKCε plays an important role in the cardioprotection of isoflurane in myocardium I/R injury.     

Inhibitory Effect of Resveratrol against Duck Enteritis Virus In Vitro

Duck viral enteritis (DVE) is an acute, contagious herpesvirus infection of ducks, geese, and swans of all ages and species. This disease has been responsible for significant economic losses in domestic and wild waterfowl as a result of mortality, and decreased egg production. Resveratrol is a naturally occurring phytoalexin in specific plants and exhibits inhibitory activity against many kinds of virus. In this paper, resveratrol was found to inhibit duck enteritis virus (DEV) replication in a dose-dependent manner, with a 50% inhibition concentration of 3.85 μg/mL. The inhibition in virus multiplication in the presence of resveratrol was not attributed to direct inactivation or inhibition of virus attachment to the host cells, but to the inhibition of viral multiplication in host cells. The assay of the time of addition limited the drug effect during the first 8 h of infection. This conclusion was supported by the ultrastructure images of the early stage of DEV infection, which showed that the replication of virus nucleic acid and the formation of the capsid in the cell nucleus were suppressed. In the indirect immunofluorescence assay, proteins expression in DEV infected duck embryo fibroblasts (DEFs) within 24 h post-infection (p.i.) was also effectively suppressed by resveratrol. In summary, the resveratrol has a good activity against DEV infection in vitro, which could be attributed to that fact that several essential immediate early viral proteins for virus replication were impacted by resveratrol.     

The Effects of p38 MAPK Inhibition Combined with G-CSF Administration on the Hematoimmune System in Mice with Irradiation Injury

The acute and residual (or long-term) bone marrow (BM) injury induced by ionizing radiation (IR) is a major clinic concern for patients receiving conventional radiotherapy and victims accidentally exposed to a moderate-to-high dose of IR. In this study, we investigated the effects of the treatment with the p38 inhibitor SB203580 (SB) and/or granulocyte colony-stimulating factor (G-CSF) on the hematoimmune damage induced by IR in a mouse model. Specifically, C57BL/6 mice were exposed to a sublethal dose (6 Gy) of total body irradiation (TBI) and then treated with vehicle, G-CSF, SB, and G-CSF plus SB. G-CSF (1 µg/mouse) was administrated to mice by intraperitoneal (ip) injection twice a day for six successive days; SB (15 mg/kg) by ip injection every other day for 10 days. It was found that the treatment with SB and/or G-CSF significantly enhanced the recovery of various peripheral blood cell counts and the number of BM mononuclear cells 10 and 30 days after the mice were exposed to TBI compared with vehicle treatment. Moreover, SB and/or G-CSF treatment also increased the clonogenic function of BM hematopoietic progenitor cells (HPCs) and the frequency of BM lineage⁻Sca1⁺c-kit⁺ cells (LSK cells) and short-term and long term hematopoietic stem cells (HSCs) 30 days after TBI, in comparison with vehicle treated controls. However, the recovery of peripheral blood B cells and CD4⁺ and CD8⁺ T cells was not significantly affected by SB and/or G-CSF treatment. These results suggest that the treatment with SB and/or G-CSF can reduce IR-induced BM injury probably in part via promoting HSC and HPC regeneration.     

Increased Expression of Pregnancy Up-Regulated Non-Ubiquitous Calmodulin Kinase Is Associated with Poor Prognosis in Clear Cell Renal Cell Carcinoma

Purpose

The aims of this study were to evaluate the clinical significance and potential prognostic value of pregnancy up-regulated non-ubiquitous calmodulin kinase (PNCK) in clear cell renal cell carcinoma (ccRCC) patients.

Materials and Methods

The expression of PNCK mRNA was determined in 24 paired samples of ccRCCs and adjacent normal tissues using real-time RT-PCR. The expression of PNCK was determined in 248 samples of ccRCCs and 92 paired samples of adjacent normal tissues by immunohistochemical analysis. Statistical analysis was performed to define the relationship between PNCK expression and the clinical features of ccRCC.

Results

The mRNA level of PNCK was significantly higher in tumorous tissues than in the adjacent non-tumorous tissues (p<0.001). An immunohistochemical analysis of 92 paired tissue specimens showed that PNCK expression was higher in tumorous tissues than in the adjacent non-tumorous tissues (p<0.001). Moreover, there was a significant correlation between the PNCK expression and various clinicopathological parameters such as Fuhrman grade (p = 0.011), tumor size (p<0.001), T stage (p<0.001) and N stage (p = 0.015). Patients with higher PNCK expression had shorter overall survival time than those with lower PNCK expression (p<0.001). Multivariate analysis indicated that PNCK expression was an independent predictor for poor survival of ccRCC patients.

Conclusions

To our knowledge, this is the first study that determines the relationship between PNCK and prognosis in ccRCC. We found that increased PNCK expression is associated with poor prognosis in ccRCC. PNCK may represent a novel prognostic marker for ccRCC.     

Ascomycota Members Dominate Fungal Communities during Straw Residue Decomposition in Arable Soil

This study investigated the development of fungal community composition in arable soil during the degradation of straw residue. We explored the short-term responses of the fungal community over 28 days of decomposition in soil using culture-independent polymerase chain reaction in combination with a clone library and denaturing gradient gel electrophoresis (DGGE). Fungal cellobiohydrolase I (cbhI) genes in the soil were also characterized, and their diversity suggested the existence of a different cellulose decomposer. The DGGE profiles based on fungal internal transcribed spacer analysis showed different successions of fungal populations during residue decomposition. Members of Lecythophora and Sordariales were dominant in the early succession, while Hypocrea and Engyodontium were better adapted in the late succession. The succession of fungal communities might be related to changes of residue quality during decomposition. Collectively, sequences assigned to Ascomycota members were dominant at different stages of the fungal succession during decomposition, revealing that they were key drivers responsible for residue degradation in the arable soil tested.     

Clinical Features of Severe Wasp Sting Patients with Dominantly Toxic Reaction: Analysis of 1091 Cases

Background

Massive wasp stings have been greatly underestimated and have not been systematically studied. The aim of this study was to identify the clinical features and treatment strategies of severe wasp stings.

Methods and Findings

A multicenter retrospective study was undertaken in 35 hospitals and medical centers including 12 tertiary care hospitals and 23 secondary care hospitals in the Hubei Province, China. The detailed clinical data of 1091 hospitalized wasp sting patients were investigated. Over three-fourths (76.9%) of the cases had 10 or more stings and the in-hospital mortality of patients was 5.1%. Forty-eight patients died of organ injury following toxic reactions to the stings, whereas six died from anaphylactic shock. The in-hospital mortality in patients with >10 stings was higher than that of ≤10 stings (5.2% vs. 1.0%, p = 0.02). Acute kidney injury (AKI) was seen in 21.0% patients and most patients required blood purification therapy. Rhabdomyolysis was seen in 24.1% patients, hemolysis in 19.2% patients, liver injury in 30.1% patients, and coagulopathy in 22.5% patients. Regression analysis revealed that high creatinine level, shock, oliguria, and anemia were risk factors for death. Blood purification therapy was beneficial for patients with ≥20 stings and delayed hospital admission of patients (≥4 hours after sting).

Conclusions

In China, most patients with multiple wasp stings presented with toxic reactions and multiple organ dysfunction caused by the venom rather than an anaphylactic reaction. AKI is the prominent clinical manifestation of wasp stings with toxic reaction. High creatinine levels, shock, oliguria, and anemia were risk factors for death.